Many cases of aseptic meningitis or meningoencephalitis, unresponsive to antimicrobial treatments, have been reported recently in patients with established/new-onset central nervous system (CNS) inflammatory demyelinating diseases (CNSIDDs). Given the higher probability of infectious etiologies, CNSIDDs are rarely considered among the differentials in meningitis or meningoencephalitis cases. We gathered and tabulated cases of non-infectious, steroid-responsive meningitis or meningoencephalitis associated with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein-associated disease (MOGAD). This conceptual review highlights the need to bolster routine infectious workups with immunological workups in cases of meningoencephalitis or meningitis where potential autoimmune etiologies can be suspected. Although differentiating CNSIDDs with meningeal involvement from infectious meningitis may not substantially affect acute treatment strategies, long-term management and follow-up of the two are entirely different. We also discuss future research directions and hypotheses on how CNSIDDs may be associated with meningitis-like presentations, e.g. overlapping glial fibrillary acidic protein astrocytopathy or autoimmune encephalitis, alterations in regulatory T-helper cells function, and undetected viral agents.
Encephalitis , Meningitis, Aseptic , Meningoencephalitis , Neuromyelitis Optica , Humans , Neuromyelitis Optica/diagnosis , Neuromyelitis Optica/therapy , Neuromyelitis Optica/complications , Encephalitis/complications , Myelin-Oligodendrocyte Glycoprotein , Meningitis, Aseptic/etiology , Meningitis, Aseptic/complications , Meningoencephalitis/diagnosis , Meningoencephalitis/etiology , Autoantibodies
Background: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. Methods: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. Results: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. Conclusion: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients
No disponible
Humans , Male , Child, Preschool , Child , Adolescent , Young Adult , B-Lymphocytes/immunology , Common Variable Immunodeficiency/immunology , Interferon Regulatory Factors/metabolism , Flow Cytometry , Interferon Regulatory Factors/genetics , RNA, Messenger/genetics , Up-Regulation , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism
T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention
No disponible
Humans , Animals , Immune System Diseases/immunology , Immunotherapy/methods , Interleukin-9/immunology , T-Lymphocytes, Helper-Inducer/immunology , Autoimmunity
T helper 9 (TH9) cells are considered as newly classified helper T cells that have an important role in the regulation of immune responses. Since these cells preferentially produce IL-9, these cells are termed TH9 cells. Recently, the role of TH9 and its signature cytokine (IL-9) has been investigated in a wide range of diseases, including autoimmunity, allergy, infections, cancer and immunodeficiency. Herein, we review the most recent data concerning TH9 cells and IL-9 as well as their roles in disease. These insights suggest that TH9 cells are a future target for therapeutic intervention.
Immune System Diseases/immunology , Immunotherapy/methods , Interleukin-9/immunology , T-Lymphocytes, Helper-Inducer/immunology , Animals , Autoimmunity , Humans
BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disorder characterized by low serum levels of immunoglobulins (Igs) and recurrent infection. In most CVID patients, a defect in the differentiation of B cells into plasma cells has been observed. Several factors play an important role in the proliferation and differentiation of B cells, including IRF4 and XBP1 transcription factors. METHODS: In the present study we investigated the expression of IRF4 and XBP1 in the B-cells of CVID and healthy controls (HCs). For this purpose, we assessed the expression of IRF4 and XBP1 at both mRNA and protein levels by real time-PCR and flow cytometry, respectively. RESULTS: We found that IRF4 expression was significantly increased in CVID patients compared with controls. Although the XBP1 protein level was lower in patients in comparison to controls, this difference was not significant. CONCLUSION: Taken together, increased IRF4 expression could be involved in defective functions of B cells in CVID patients.
B-Lymphocytes/immunology , Common Variable Immunodeficiency/immunology , Interferon Regulatory Factors/metabolism , Adolescent , Adult , Child , Child, Preschool , Female , Flow Cytometry , Humans , Interferon Regulatory Factors/genetics , Male , RNA, Messenger/genetics , Up-Regulation , X-Box Binding Protein 1/genetics , X-Box Binding Protein 1/metabolism , Young Adult
BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications
No disponible
Humans , Male , Female , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/immunology , Common Variable Immunodeficiency/pathology , B-Lymphocyte Subsets/immunology , B-Lymphocyte Subsets/pathology , Common Variable Immunodeficiency , Immunoglobulin M/immunology , Flow Cytometry/methods , Flow Cytometry , Enzyme-Linked Immunosorbent Assay/methods , Vaccination/methods
BACKGROUND: Common variable immunodeficiency (CVID) is a heterogeneous disease, characterised by hypogammaglobulinaemia leading to recurrent infections and various complications. The aim of this study was to classify CVID patients based on four known classifications (Paris, Freiburg, EUROclass, and B-cell patterns) by measurement of B-cell subsets and to assess the relation of each classification with clinical manifestations. METHODS: We measured all B-cell subsets as both absolute count and percentage in 30 CVID patients and 30 healthy individuals using four-colour flow cytometry. Moreover, we evaluated antibody responses to pneumococcal vaccine in patients. RESULTS: A significant reduction in percentage of terminal B-cell subsets (total, marginal zone-like, switched memory, IgM-only memory, total memory B-cells and plasmablast) and absolute count of all B-cell subsets along with a strong increase in CD21low B-cells has been observed in patients. Patients with splenomegaly and hepatomegaly clustered in group Ia, smB+21low and group 1 based on known classifications, and significantly tended to have a decreased transitional and marginal zone-like B-cells count, as well as an increase in CD21low B-cell counts. Patients with lymphadenopathy, bronchiectasis and allergy had a significant decrease in absolute count of total memory, switched memory and total B-cells, respectively. CONCLUSION: Classification of patients could provide useful information to guide clinicians in long-term follow-up of CVID patients. Our data demonstrate that it may be more accurate to use absolute counts of B-cell subpopulations in CVID patients because absolute counts of B-cell subsets are more associated with clinical manifestations compared with their percentage and also four known classifications.
B-Lymphocyte Subsets/immunology , Common Variable Immunodeficiency/immunology , Adolescent , Adult , Bronchiectasis , Child , Common Variable Immunodeficiency/classification , Common Variable Immunodeficiency/physiopathology , Female , Hepatomegaly , Humans , Immunologic Memory , Immunophenotyping , Lymphadenopathy , Lymphocyte Count , Male , Middle Aged , Receptors, Complement 3d/metabolism , Splenomegaly , Young Adult
Multiple sclerosis (MS) is an organ-specific autoimmune disease in central nervous system, affecting about 2.5 million people around the world. Probable involvement of two newly identified immunoregulator molecules, TIM-1 and TIM-3, has been reported in autoimmune diseases. In this study, for the first time, the association of TIM-1 5383-5397ins/del and TIM-3 -1541C>T polymorphisms with MS in an Iranian population was considered. The results of our study showed that there is no significant association between TIM-1 5383-5397ins/del and MS (P = 0.38); however, the frequency of CT genotype of TIM-3 -1541C>T in patient group was significantly higher than the control group, and there was a significant association between CT genotype and MS (P = 0.009, OR = 4.08).
Genetic Association Studies , Hepatitis A Virus Cellular Receptor 1/genetics , Hepatitis A Virus Cellular Receptor 2/genetics , Multiple Sclerosis/genetics , Adult , Female , Genetic Predisposition to Disease , Genotype , Humans , INDEL Mutation , Iran , Male , Multiple Sclerosis/pathology , Polymorphism, Single Nucleotide
TIM (T-cell immunoglobulin (Ig) and mucin domain)-1, one of the members of TIM family, expresses on Th2 cells and promotes the production of Th2 signature cytokines. This can increase a series of responses in these cells which could be one of the causes of asthma or asthma-related phenotypes. The aim of this study was to investigate whether a TIM-1 promoter single nucleotide polymorphism (SNP), -416 G>C, is associated with asthma in Iranian population. In this case-control study, existence of the -416 G>C polymorphism was assessed using polymerase chain reaction (PCR) and restriction fragment length polymorphism (RFLP) in 300 patients with asthma (97 atopic, 203 nonatopic) and 309 healthy volunteers. Additionally, the relationship between these polymorphism genotypes and total serum IgE levels in this Iranian population was evaluated. We discovered a significant association between the -416 G>C polymorphism and atopic asthma susceptibility in the population, but this SNP showed no connection with nonatopic asthma (P < 0.05). However, our results showed significant relation between this polymorphism and serum IgE level (P < 0.05). Our results suggest that -416 G>C polymorphism in TIM-1 gene could be a predisposing factor for atopic asthma in Iranian population, and CC genotype of this SNP can be associated with increased level of IgE in patients with asthma in the same population.
Asthma/genetics , Genetic Association Studies , Genetic Predisposition to Disease , Membrane Glycoproteins/genetics , Receptors, Virus/genetics , Adult , Asthma/pathology , Female , Genotype , Hepatitis A Virus Cellular Receptor 1 , Humans , Immunoglobulin E/genetics , Iran , Male , Middle Aged , Polymorphism, Single Nucleotide , Promoter Regions, Genetic
BACKGROUND AND OBJECTIVE: The aim of this study was to identify the specific markers of T helper 17 (Th17) cells and their variations in people suffering from chronic periodontal disease in comparison with normal control subjects. MATERIAL AND METHODS: In 30 patients with periodontitis and 30 normal control subjects, the mRNA expressions of interleukin (IL)-17A and retinoic orphan receptor C2 (RORC2) were measured by quantitative RT-PCR. The protein levels of IL-17A and RORC2 were also evaluated by immunohistochemistry. The levels of these markers were compared between healthy and diseased periodontal tissues by the Mann-Whitney U-test. RESULTS: In periodontal lesions, IL-17A and RORC2 were significantly overexpressed compared with normal tissues. According to our immunohistochemical analysis, the number of IL-17A-positive cells and RORC2-positive cells was significantly greater in periodontal lesions compared with control sites. Moreover, there was a positive correlation between the presence of IL-17A and RORC2 transcript and protein content levels in the gingiva of diseased patients. CONCLUSION: The results demonstrated a significant increase in the number of some specific markers of Th17 cells in patients suffering from periodontal disease in comparison with normal control subjects.
Chronic Periodontitis/immunology , Interleukin-17/biosynthesis , Nuclear Receptor Subfamily 1, Group F, Member 3/biosynthesis , Th17 Cells/metabolism , Adult , Biomarkers , Case-Control Studies , Female , Humans , Male , Middle Aged , Statistics, Nonparametric , Th17 Cells/chemistry , Young Adult
